Degenerative diseases of cartilage, e.g., osteoarthritis, are among the most prevalent and debilitating chronic health problems in the United States. Treatment of degenerative cartilage diseases is a particular clinical challenge because of the limited capacity of the tissue for self-repair. Because of their ability to differentiate into multiple cell types and their unlimited capacity for self-renewal, human embryonic stem cells (hESCs) are a potentially powerful tool for the repair of cartilage defects. Fulfilling the potential of hESCs for repair of diseased and damaged cartilage requires developing methods for directing their differentiation into the chondrogenic lineage.
Although several culture systems have been developed in which ESC-derived cells differentiate to various degrees into chondrocytes, in these systems chondrogenic differentiation is not uniform, and chondrocytes represent only a subpopulation of the cells that differentiate, complicating utilization of the cell population for cartilage repair. Prior to the invention described below, most of the chondrogenic differentiation protocols utilized cells of embryoid bodies (EBs) derived from ESCs. A drawback of such earlier methods is that the cellular heterogeneity of EB-derived cells hinders the ability to obtain homogeneous populations of chondrogenic cells that can be used for cartilage repair.